The -c(=x)- Is Part Of A -c(=x)x- Group, Wherein The X's Are The Same Or Diverse Chalcogens Patents (Class 546/147)
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Patent number: 5670516Abstract: This invention provides novel decahydroisoquinoline compounds which are useful as excitatory amino acid receptor antagonists and in the treatment of neurological disorders. This invention also provides synthetic methods for preparing decahydroisoquinolines, as well as, novel intermediates in the synthesis thereof.Type: GrantFiled: June 1, 1995Date of Patent: September 23, 1997Assignee: Eli Lilly and CompanyInventors: M. Brian Arnold, Nancy K. Augenstein, William H. W. Lunn, Paul L. Ornstein, Darryle D. Schoepp
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Patent number: 5665880Abstract: This invention relates to a process for the preparation of a product of the formula ##STR1## wherein R is loweralkyl; R.sub.1, is hydrogen, loweralkyl, lowercycloalkyl, lowercycloalkylloweralkyl, lowerbicycloalkyl, aryl or arylloweralyl; R.sub.2 is lower alkyl, lowercycloalkyl, lowercycloalkylloweralkyl, lowerbicycloalkyl, aryl or arylloweralkyl; or R.sub.1 and R.sub.2 taken together with the nitrogen atom to which they are attached form a group of the formula (Ia) ##STR2## wherein Y is hydrogen or loweralkyl and Z is hydrogen, loweralkyl, halogen, loweralkoxy or hydroxy; X is loweralkyl, loweralkoxy, halogen or trifluoromethyl; and m is 0, 1 or 2; or a pharmaceutically acceptable salt thereof; which process comprises(a) contacting a compound of formula (II) as defined herein with fortified hydrogen bromide to afford a compound of formula (III) as defined herein; contacting the reaction mixture containing a compound of formula (III) with either (1) an isocyanate of formula R.sub.Type: GrantFiled: October 31, 1996Date of Patent: September 9, 1997Assignee: Hoechst Marion Roussel, Inc.Inventors: Thomas B. K. Lee, Zhongli Gao
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Patent number: 5663348Abstract: An optically active .beta.-aminoalkoxyborane complex of the formula (I): ##STR1## wherein R.sup.1 is C.sub.1 -C.sub.8 alkyl, C.sub.3 -C.sub.7 cycloalkyl, C.sub.7 -C.sub.11 aralkyl or C.sub.6 -C.sub.10 aryl, R.sup.2 is hydrogen, C.sub.1 -C.sub.8 alkyl, C.sub.3 -C.sub.7 cycloalkyl or C.sub.7 -C.sub.11 aralkyl, or R.sup.1 and R.sup.2 together form (CH.sub.2).sub.n wherein n is 3 or 4, and Ar is naphthyl, anthryl or phenanthryl, which may be substituted by from 1 to 3 substituents selected from the group consisting of halogen, nitro, C.sub.1 -C.sub.6 alkyl, C.sub.3 -C.sub.7 cycloalkyl, C.sub.2 -C.sub.6 alkenyl, C.sub.2 -C.sub.6 alkynyl, C.sub.7 -C.sub.11 aralkyl, C.sub.6 -C.sub.10 aryl, C.sub.1 -C.sub.6 alkoxy and styrene polymer substituents.Type: GrantFiled: July 19, 1995Date of Patent: September 2, 1997Assignee: Nissan Chemical Industries Ltd.Inventors: Hiroshi Kashihara, Mikio Suzuki, Yoshio Ohara
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Patent number: 5661157Abstract: Compound of general formula I ##STR1## wherein A denotes a benzo, indolo or thienyl group;B denotes the group --0--, --S-- or --CHR.sup.5 --, wherein R.sup.5 is hydrogen, (C.sub.1-6)alkyl, phenyl or benzyl;R.sup.3 denotes 2- or 3-thienyl, (C.sub.4-7)cycloalkyl, (C.sub.4-6)cycloalkyl(C.sub.1-5)alkyl or ##STR2## wherein R is (C.sub.1-4)alkyl, hydroxy, --N.sub.3, halogen (F, Cl, Br, I), CF.sub.3 or (C.sub.1-4)alkoxy,u is 0, 1, 2 or 3, andm, R.sup.2, R.sup.4, R.sup.7, R.sup.8 and R.sup.9 are as defined in the specification, as well as pharmaceutical preparations containing these compounds and the pharmaceutical use thereof.Type: GrantFiled: December 21, 1994Date of Patent: August 26, 1997Assignee: Boehringer Ingelheim KGInventors: Otto Roos, Walter Losel, Dietrich Arndts
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Patent number: 5661161Abstract: The present invention comprises analogs of the CAAX motif of the protein Ras that is modified by farnesylation in vivo. These CAAX analogs inhibit farnesyl-protein transferase. Furthermore, these CAAX analogues differ from those previously described as inhibitors of farnesyl-protein transferase in that they do not have a thiol moiety. The lack of the thiol offers unique advantages in terms of improved pharmacokinetic behavior in animals, prevention of thiol-dependent chemical reactions, such as rapid antoxidation and disulfide formation with endogenous thiols, and reduced systemic toxicity. Further contained in this invention are chemotherapeutic compositions containing these farnesyl transferase inhibitors and methods for their production.Type: GrantFiled: September 14, 1995Date of Patent: August 26, 1997Assignee: Merck & Co., Inc.Inventors: Neville J. Anthony, Terrence M. Ciccarone, S. Jane deSolms, Samuel L. Graham, Gerald E. Stokker, Catherine M. Wiscount
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Patent number: 5658933Abstract: The invention relates to compounds of the formula I, ##STR1## to a process for their preparation and to their use as pharmaceuticals. The compounds are employed, in particular, as ester prodrugs of prolyl hydroxylase inhibitors for inhibiting collagen biosynthesis and as fibrosuppressive agents.Type: GrantFiled: October 31, 1994Date of Patent: August 19, 1997Assignee: Hoechst AktiengesellschaftInventors: Klaus Weidmann, Karl-Heinz Baringhaus, Georg Tschank, Martin Bickel
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Patent number: 5648492Abstract: This invention provides novel decahydroisoquinoline compounds which are useful as excitatory amino acid receptor antagonists and in the treatment of neurological disorders. This invention also provides synthetic methods for preparing decahydroisoquinolines, as well as, novel intermediates in the synthesis thereof.Type: GrantFiled: June 1, 1995Date of Patent: July 15, 1997Assignee: Eli Lilly and CompanyInventors: M. Brian Arnold, Carl F. Bertsch, Marvin M. Hansen, Allen R. Harkness, Bret Huff, Michael J. Martinelli, Paul L. Ornstein
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Patent number: 5646121Abstract: The present invention relates to novel pseudopeptides with antiviral activity of the general formula (I) ##STR1## in which the substituents have the meaning given in the description, to a process for their preparation, and to their use as antiviral agents, especially against cytomegaloviruses.Type: GrantFiled: September 7, 1994Date of Patent: July 8, 1997Assignee: Bayer AktiengesellschaftInventors: Dieter Habich, Thomas-J. Schulze, Jurgen Reefschlager, Jutta Hansen, Rainer Neumann, Gert Streissle, Arnold Paessens
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Patent number: 5646161Abstract: Heteroarylpiperidines, pyrrolidines, and piperazines are useful as antipsychotic and analgesic agents. The compounds are especially useful for treating psychoses by administering to a mammal a psychoses-treating effective amount of one of the compounds. Depot derivatives of the compounds are useful for providing long acting effects of the compounds. The compounds are also useful as analgesics by administering a pain-relieving effective amount of one of the compounds to a mammal.Type: GrantFiled: June 6, 1995Date of Patent: July 8, 1997Assignee: Hoechst-Marion-Roussel, Inc.Inventors: Edward J. Glamkowski, Yulin Chiang
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Patent number: 5643926Abstract: Novel substituted pyrazolidinones have been found to exhibit significant binding to cholecystokinin (CCK) receptors and gastrin receptors in the brain and/or peripheral sites such as the pancreas, stomach, and ileum. The pyrazolidinones are CCK and gastrin receptor antagonists and find therapeutic application in the treatment of gastrointestinal disorders, central nervous system disorders and for appetite regulation in warm-blood vertebrates. Pharmaceutical formulations for such indications are described.Type: GrantFiled: January 19, 1994Date of Patent: July 1, 1997Assignee: Eli Lilly and CompanyInventors: Raymond F. Brown, J. Jeffry Howbert, Karen L. Lobb, David A. Neel, Jon K. Reel, Beverley Greenwood
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Patent number: 5643924Abstract: N-heterocyclic moiety containing hydroxyethylamine compounds are effective as retroviral protease inhibitors, and in particular as inhibitors of HIV protease.Type: GrantFiled: May 31, 1995Date of Patent: July 1, 1997Assignee: Monsanto Company of St. LouisInventors: John J. Talley, Daniel P. Getman, Gary A. DeCrescenzo, Kathryn L. Reed, Ko-Chung Lin, John Nicholas Freskos, Michael Clare, Donald Joseph Rogier, Jr., Robert M. Heintz, Michael L. Vazquez, Richard A. Mueller
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Patent number: 5639885Abstract: The invention provides novel amino acids and peptides containing them which comprise a dihydropyridine.revreaction.pyridinium salt-type redox system and which provide site-specific and sustained delivery of pharmacologically active peptides to the brain. These new amino acids contain a redox system appended directly or via an alkylene bridge to the carbon atom adjacent to the carboxyl carbon and may be incorporated into a peptide chain at a variety of positions, including non-terminal positions.Type: GrantFiled: February 28, 1995Date of Patent: June 17, 1997Assignee: University of FloridaInventor: Nicholas S. Bodor
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Antimalarial naphthylisoquinoline alkaloids and pharmaceutical compositions and medical uses thereof
Patent number: 5639761Abstract: The present invention provides antimalarial pharmaceutical compositions containing antimalarial naphthylisoquinoline alkaloids or antimalarial derivatives thereof, useful new antimalarial naphthylisoquinoline alkaloid derivatives, methods for obtaining such derivatives, and methods of using such antimalarial compounds for the prevention of malaria infections in mammals and for treating mammals with malarial infections. The antimalarial compounds of the present invention inhibit the reproduction and cytopathicity of Plasmodium sp. parasites in vitro and in vivo.Type: GrantFiled: February 14, 1994Date of Patent: June 17, 1997Assignee: The United States of America as represented by the Secretary of the Department of Health and Human ServicesInventors: Guido Francois, Gerhard Bringmann, J. David Phillipson, Michael R. Boyd, Laurent Ake Assi, Christoph Schneider, Georges Timperman -
Patent number: 5637712Abstract: This invention provides novel decahydroisoquinoline compounds which are useful as excitatory amino acid receptor antagonists and in the treatment of neurological disorders. This invention also provides synthetic methods for preparing decahydroisoquinolines, as well as, novel intermediates in the synthesis thereof.Type: GrantFiled: November 21, 1994Date of Patent: June 10, 1997Assignee: Eli Lilly and CompanyInventors: Carl F. Bertsch, Bret Huff, Michael J. Martinelli
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Patent number: 5633231Abstract: The present invention relates to valine-containing, substituted pseudopeptides of the general formula (I) ##STR1## in which the substituents have the meaning given in the description, to processes for their preparation, and to their use as anti-viral agents, in particular against cytomegaloviruses.Type: GrantFiled: September 7, 1994Date of Patent: May 27, 1997Assignee: Bayer AktiengesellschaftInventors: Dieter Habich, Thomas J. Schulze, Jurgen Reefschlager, Jutta Hansen, Rainer Neumann, Gert Streissle, Arnold Paessens
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Patent number: 5629321Abstract: The invention relates to a novel compound which is represented by the formula (1) and has an excellent platelet aggregation inhibiting action based on fibrinogen antagonism. The platelet aggregation inhibitor containing the compound of the formula (1) as an effective ingredient are effective for prevention and curing of thrombosis and restenosis or reocclusion after percutaneous transluminal coronary angioplasty or percutaneous transluminal coronary recanalization.Type: GrantFiled: October 18, 1995Date of Patent: May 13, 1997Assignee: Mitsui Toatsu Chemicals, Inc.Inventors: Kunio Okumura, Isao Yokoyama, Toshiyuki Shimazaki, Michihiko Miyamoto, Hiroyuki Yamashita, Kenji Kibayashi, Takanori Yutaka, Kouhei Yazawa
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Patent number: 5627282Abstract: This invention relates to the preparation of optically pure tetrahydro-3-isoquinolinecarboxylic acid derivative of formula (III) which comprises the reaction of optically pure phenylalanine derivative of formula (I) with a formaldehyde precursor, such as formaline, trioxane, dialkoxymethane, or paraformaldehyde, for about 10 hours to 60 hours at about 40 .degree. C. to about 60 .degree. C. in concentrated hydrochloric acid to give the compound of formula (II), followed by neutralization in hot water at about 70 .degree. C. to about 100 .degree. C. with a base, such as ammonium hydroxide, potassium carbonate, sodium carbonate, sodium hydroxide or potassium hydroxide, according to the following reaction scheme.Type: GrantFiled: January 3, 1996Date of Patent: May 6, 1997Assignee: Yukong LimitedInventors: Taesoo Kwon, Francis J. Taplin
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Patent number: 5624936Abstract: The present invention comprises analogs of the CA.sup.1 A.sup.2 X motif of the protein Ras that is modified by farnesylation in vivo. These CA.sup.1 A.sup.2 X analogs inhibit the farnesyl-protein transferase and the farnesylation of certain proteins. Furthermore, these CA.sup.1 A.sup.2 X analogs differ from those previously described as inhibitors of farnesyl-protein transferase in that they do not have a thiol moiety. The lack of the thiol offers unique advantages in terms of improved pharmacokinetic behavior in animals, prevention of thiol-dependent chemical reactions, such as rapid autoxidation and disulfide formation with endogenous thiols, and reduced systemic toxicity. The compounds of the instant invention also incorporate a cyclic amine moiety in the A.sup.2 position of the motif. Further contained in this invention are chemotherapeutic compositions containing these farnesyl transferase inhibitors and methods for their production.Type: GrantFiled: February 13, 1996Date of Patent: April 29, 1997Assignee: Merck & Co., Inc.Inventor: S. Jane deSolms
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Patent number: 5618939Abstract: A process is disclosed for making a chiral compound of the formula ##STR1## comprising reacting an epoxide compound of the formula ##STR2## and an amide of the formula ##STR3## in the presence of a strong base at a low temperature.Type: GrantFiled: June 7, 1995Date of Patent: April 8, 1997Assignee: Merck & Co., Inc.Inventors: David Askin, Paul Reider, Kai Rossen, Richard J. Varsolona, Ralph P. Volante, Kenneth M. Wells
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Patent number: 5610307Abstract: A substantially pure L-isomer of (3S) 1,2,3,4-tetrahydro-isoquinoline is produced from an optically enriched mixture by cyclizing D- or L-phenylalanine using a solution of formaldehyde and hydrochloric acid, adjusting the pH of the mixture to yield the neutral free acid form and treating the mixture with dilute acetic acid of from about 5.0 wt/wt % to about 25 wt/wt %. The mixture is then refluxed at 80.degree. C. to 95.degree. C. and cooled to about 10.degree. C. to yield amorphous powdery solid material.Type: GrantFiled: March 14, 1995Date of Patent: March 11, 1997Assignee: The Nutra Sweet CompanyInventor: Robert A. Erickson
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Patent number: 5607624Abstract: A process for the preparation of compounds of formula I ##STR1## wherein the general symbols are as defined in claim 1, which comprises reacting a compound of formula III ##STR2## wherein the general symbols are as defined in claim 1, with a compound of formula IV[H].sub.n --R.sub.1 (IV).Type: GrantFiled: September 12, 1994Date of Patent: March 4, 1997Assignee: Ciba-Geigy CorporationInventors: Peter Nesvadba, Samuel Evans, Ralf Schmitt
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Patent number: 5606062Abstract: This invention provides novel decahydroisoquinoline compounds which are useful as excitatory amino acid receptor antagonists and in the treatment of neurological disorders. This invention also provides synthetic methods for preparing decahydroisoquinolines, as well as, novel intermediates in the synthesis thereof.Type: GrantFiled: June 1, 1995Date of Patent: February 25, 1997Assignee: Eli Lilly and CompanyInventor: Bret Huff
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Patent number: 5605926Abstract: The present invention relates to new trifluoromethyl-containing pseudopeptides of the general formula (I) ##STR1## in which W, A, B, D, E, R.sub.1, R.sub.2 and R.sub.3 have the meaning as outlined of their making and use as pharmaceuticals.Type: GrantFiled: April 10, 1995Date of Patent: February 25, 1997Assignee: Bayer AktiengesellschaftInventors: Dieter H abich, Wolfgang R oben, Jutta Hansen, Arnold Paessens
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Patent number: 5602255Abstract: The present invention relates to a process for producing 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid compounds or salts thereof represented by the following formula (II): ##STR1## wherein R.sup.1, R.sup.2 and R.sup.3 independently represent hydrogen, hydroxy or lower alkoxy, and R.sup.4 represent hydrogen, lower alkyl, aryl or aralkyl, the process comprising, allowing phenylalanine compounds to react with formaldehyde or paraformaldehyde in the presence of sulfuric acid or hydrobromic acid, the phenylalanine compounds being represented by the following formula (I): ##STR2## wherein R.sup.1, R.sup.2, R.sup.3 and R.sup.4 have the same meaning as defined above.Type: GrantFiled: April 4, 1995Date of Patent: February 11, 1997Assignee: Kyowa Hakko Kogyo Co., Ltd.Inventors: Yukihiro Kuge, Toru Sugaya, Shinji Tomioka
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Patent number: 5602236Abstract: Metal-containing steroid mimic complexes are provided. Compositions containing a metal ion incorporated into a steroid skeleton structure and ligands useful in the preparation of such compositions are also provided. The metal ion is preferably a radionuclide, such as technetium, rhenium or gallium. Methods for using the metal complexes for diagnostic and therapeutic purposes are further provided.Type: GrantFiled: April 8, 1994Date of Patent: February 11, 1997Assignee: Mallinckrodt Medical, Inc.Inventor: Raghavan Rajagopalan
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Patent number: 5593967Abstract: Novel cholecystokinin antagonists useful as agents in the treatment of obesity, hypersecretion of gastric acid in the gut, gastrin-dependent tumors, or as antipsychotics are disclosed. Further, the compounds are antianxiety agents and antiulcer agents. They are agents useful for preventing the response to the withdrawal from chronic treatment with use of nicotine, diazepam, alcohol, cocaine, coffee, or opioids. The compounds of the invention are also useful in treating and/or preventing panic. Also disclosed are pharmaceutical compositions and methods of treatment using the antagonists as well as processes for preparing them and novel intermediates useful in their preparation. An additional feature of the invention is the use of the subject compounds in diagnostic compositions.Type: GrantFiled: April 1, 1993Date of Patent: January 14, 1997Assignee: Warner-Lambert CompanyInventors: David C. Horwell, Edward Roberts, Ann Holmes, Janak K. Padia, William H. Roark, Bruce D. Roth, Bharat K. Trivedi, Jurgen Kleinschroth, David C. Rees, Reginald S. Richardson
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Patent number: 5587481Abstract: Methods for preparing (S)-N-tert-butyl-1,2,3,4-tetrahydro-3-isoquinoline-carboxamide ("tic-c"), and converting tic-c to (S)-decahydroisoquinoline-3-carboxylic acid t-butylamide ("tic-d") are disclosed. The initial step in the formation of tic-c involves the phosgenation of a substituted tetrahydroisoquinoline to form an N-carboxy anhydride. Tic-d is used as an intermediate in the synthesis of known compounds having pharmaceutical activity.Type: GrantFiled: February 20, 1996Date of Patent: December 24, 1996Assignee: The Monsanto CompanyInventors: David R. Allen, Scott Jenkins, Loraine Klein, Robert Erickson, Diane Froen
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Patent number: 5585486Abstract: Disclosed are compounds of the formula (I) and pharmaceutically acceptable salts thereof: ##STR1## wherein R.sub.1 is (CR.sub.5 R.sub.6).sub.n, (CR.sub.5 R.sub.6).sub.n,-aryl, (CR.sub.5 R.sub.6).sub.n -heteroaryl, X-(CR.sub.5 R.sub.6).sub.n, X-(CR.sub.5 R.sub.6).sub.n -aryl or X-(CR.sub.5 R.sub.6).sub.n -heteroaryl wherein aryl and heteroaryl may be optionally substituted;X is 0 or NR.sub.5 ;R.sub.5 and R.sub.6 are independently H or lower alkyl;R.sub.2 is H, halo, lower alkyl or (CR.sub.5 R.sub.6).sub.n -aryl;R.sub.3 and R.sub.4 are independently H or alkyl;A is a D or L isomer of an amino acid selected from the group consisting of alanine, valine, leucine, isoleucine, proline, phenylalanine, glycine, tyrosine, methionine, asparagine, glutamine, aspartic acid, glutamic acid, lysine, arginine, histidine and .beta.-thienylalanine;Z is CH.sub.2 or O; andn is 0-4;pharmaceutical compositions containing the compounds; and a method for inhibiting interleukin-1.beta.Type: GrantFiled: May 12, 1995Date of Patent: December 17, 1996Assignee: Sterling Winthrop Inc.Inventors: Roland E. Dolle, Todd L. Graybill, Gary J. Speier, Catherine P. Prouty, Stanley J. Schmidt
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Patent number: 5580999Abstract: Novel alcohols of the formula ##STR1## wherein R.sup.a is azido or phthalimido, R.sup.4 is alkyl, cycloalkyl, cycloalkylalkyl, aryl or aralkyl, R.sup.7 and R.sup.8 together are a trimethylene or tetramethylene group which is optionally substituted by hydroxy, alkoxycarbonylamino or acylamino or in which one --CH.sub.2 -- group is replaced by --NH--, -N(alkoxycarbonyl)-,-N(acyl)- or --S--or which carries a fused cycloalkane, aromatic or heteroaromatic ring, and R.sup.9 is alkoxycarbonyl, monoalkylcarbamoyl, monoaralkylcarbamoyl, monoarylcarbamoyl or a group of the formula ##STR2## in which R.sup.10 and R.sup.11 each is alkyl, are described along with a process for their manufacture. These alcohols are useful as intermediates, for example in the manufacture of amino acid derivatives having antiviral activity.Type: GrantFiled: May 12, 1995Date of Patent: December 3, 1996Assignee: Hoffmann-La Roche Inc.Inventors: Kevin E. B. Parkes, Sally Redshaw, Gareth J. Thomas
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Patent number: 5580982Abstract: This application relates to compounds of the formula ##STR1## wherein R.sup.1, X, Y and n are as defined in the specification; and pharmaceutically acceptable addition salts thereof and optical and geometric isomers or racemic mixtures thereof; which compounds are useful for the treatment of various memory dysfunctions characterized by a decreased cholinergic function such as Alzheimer's disease. Compounds of this invention also inhibit monoamine oxidase and hence are useful as antidepressants.Type: GrantFiled: June 6, 1995Date of Patent: December 3, 1996Assignee: Hoechst Marion Roussel Inc.Inventors: Gerard J. O'Malley, Mark G. Palermo
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Patent number: 5578730Abstract: A process for the production of a .beta.-aminoalcohol 2-[3(S)-amino-2-hydroxy-4-phenylbutyl]-N-tert.butyl-decahydro-(4aS,8aS)-is oquinoline-3(S)-carboxamide of the formula ##STR1## via the oxazolidinone corresponding to the aminoalcohol 10 which process comprises refluxing a sulphonic acid ester with a carboxamide in the presence of a base and a solvent.Type: GrantFiled: March 9, 1995Date of Patent: November 26, 1996Assignee: Hoffmann-La Roche Inc.Inventor: Hans Hilpert
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Patent number: 5576435Abstract: The present invention provides novel intermediates which are useful for the preparation of excitatory amino acid receptor antagonists. Further provided is a process to enatioselectively prepare hydroisoquinoline compounds with central nervous system activity.Type: GrantFiled: May 19, 1995Date of Patent: November 19, 1996Assignee: Eli Lilly and CompanyInventors: Anita Melikian-Badalian, Paul L. Ornstein
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Patent number: 5571821Abstract: Sulfonamides and methods using these sulfonamides for inhibiting the binding of an endothelin peptide to an endothelin receptor by contacting the receptor with the sulfonamide are provided. Methods for treating endothelin-mediated disorders by administering effective amounts of one or more of these sulfonamides or prodrugs thereof that inhibit or increase the activity of endothelin are also provided. The sulfonamides have formula I: ##STR1## in which Ar.sup.1 is a 3- or 5-isoxazolyl and Ar.sup.2 is selected from among alkyl, including straight and branched chains, aromatic rings, fused aromatic rings and heterocyclic rings, including 5-membered heterocycles with one, two or more heteroatoms and fused ring analogs thereof and 6-membered rings with one, two or more heteroatoms and fused ring analogs thereof. Ar.sup.2 is preferably thiophenyl, furyl, pyrrolyl, naphthyl, and phenyl. Compounds in which Ar.sup.Type: GrantFiled: May 20, 1994Date of Patent: November 5, 1996Assignee: Texas Biotechnology CorporationInventors: Ming Fai Chan, Bore G. Raju, Adam Kois, Erik J. Verner, Chengde Wu, Rosario S. Castillo, Venkatachalapathi Yalamoori, Vitukudi N. Balaji, Kalyanaraman Ramnarayan
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Patent number: 5571919Abstract: The present invention provides methods of preparing dimeric naphthylisoquinoline alkaloids by coupling together two monomeric naphthylisoquinoline alkaloids, each of which may be the same or different, and one, both, or neither of which may possess a C-8' to C-5 naphthalene/isoquinoline linkage, to form homodimers or heterodimers, including the antiviral michellamines. The present invention also provides new, medically useful homodimeric and heterodimeric naphthylisoquinoline compounds and derivatives thereof.Type: GrantFiled: July 22, 1994Date of Patent: November 5, 1996Assignee: The United States of America as represented by the Department of Health and Human ServicesInventors: Gerhard Bringmann, Sven Harmsen, Michael R. Boyd
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Patent number: 5569762Abstract: The disclosure describes an improved process for producing optically active compounds of Formula II or III, which compounds are useful as intermediates for preparing compounds active as inhibitors of retroviral protease enzymes: ##STR1## wherein R.sub.1, R.sub.50 and Z are described in the specification. The improved process includes either synthesis of diastereomeric iodolactones which are separated prior to conversion to compounds of Formula II or III or synthesis of an epoxide which is converted directly to compounds of Formula II and III.Type: GrantFiled: March 22, 1995Date of Patent: October 29, 1996Assignee: American Cyanamid CompanyInventors: Allan Wissner, Michael P. Trova
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Patent number: 5545835Abstract: There are provided 5,6-disubstituted-3-pyridylmethyl ammonium halide compounds, a method for the preparation thereof and the use thereof for the preparation of 5-(substituted methyl)-2,3-pylidinedicarboxylic acids.Type: GrantFiled: November 4, 1994Date of Patent: August 13, 1996Assignee: American Cyanamid CompanyInventor: Henry L. Strong
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Patent number: 5543423Abstract: The present invention relates to compounds that can maintain, increase, or restore sensitivity of cells to therapeutic or prophylactic agents. This invention also relates to pharmaceutical compositions comprising these compounds. The compounds and pharmaceutical compositions of this invention are particularly well-suited for treatment of multi-drug resistant cells, for prevention of the development of multi-drug resistance, and for use in multi-drug resistant cancer therapy.Type: GrantFiled: January 23, 1995Date of Patent: August 6, 1996Assignee: Vertex Pharmaceuticals, IncorporatedInventors: Robert E. Zelle, Matthew W. Harding
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Patent number: 5532243Abstract: There are provided nitrogen-containing bicyclic compounds, pharmaceutical compositions containing these compounds and methods of using these compounds to treat physiological or drug-induced psychosis or diskinesia in a mammal.Type: GrantFiled: February 14, 1992Date of Patent: July 2, 1996Assignee: The DuPont Merck Pharmaceutical CompanyInventor: Paul J. Gilligan
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Patent number: 5529978Abstract: Certain N-acetonyl-substituted-amides of the formula: ##STR1## wherein A is a heterocycle, a phenylalkyl, a phenylalkoxy, naphthyl, cycloalkyl, alkoxyalkyl, alkyl, haloalkyl or alkenyl group; X, Y and Z are selected from the group consisting of hydrogen, halo, cyano, thiocyano, isothiocyano, methylsulfonyloxy, thio(C.sub.1 -C.sub.2)alkyl, (C.sub.1 -C.sub.2)alkoxy, carbamoyl, dithiocarbamoyl, hydroxy, azide, trifluoromethylcarboxy, (C.sub.1 -C.sub.4)alkylcarbonyloxy, phenylcarbonyloxy, phenoxy, thiophenyl, imidazolyl or triazolyl group as described herein; R.sup.1 and R.sup.2 are each independently a hydrogen atom or a (C.sub.1 -C.sub.6)alkyl group; and compositions containing these amides are fungicidally active, particularly against phytopathogenic fungi.Type: GrantFiled: May 3, 1994Date of Patent: June 25, 1996Assignee: Rohm and Haas CompanyInventor: Ashok K. Sharma
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Patent number: 5527810Abstract: This invention provides novel decahydroisoquinoline compounds which are useful as excitatory amino acid receptor antagonists and in the treatment of neurological disorders. This invention also provides synthetic methods for preparing decahydroisoquinolines.Type: GrantFiled: June 8, 1994Date of Patent: June 18, 1996Assignee: Eli Lilly and CompanyInventor: Paul L. Ornstein
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Patent number: 5523306Abstract: Novel .alpha.-substituted Trp dipeptoid derivatives cyclized at the C-terminal useful as agents in the treatment of obesity, hypersecretion of gastric acid in the gut, gastrin-dependent tumors, or as antipsychotics are disclosed. Further, the compounds are antianxiety agents and antiulcer agents. They are agents useful for preventing the response to the withdrawal from chronic treatment with or use of nicotine, diazepam, alcohol, cocaine, caffeine, or opioids. The compounds of the invention are also useful in treating and/or preventing panic attacks. Also disclosed are pharmaceutical compositions and methods of treatment using the compounds as well as processes for preparing them and novel intermediates useful in their preparation. An additional feature of the invention is the use of the compounds in diagnostic compositions.Type: GrantFiled: December 5, 1994Date of Patent: June 4, 1996Assignee: Warner-Lambert CompanyInventors: David C. Horwell, Martyn C. Pritchard, Edward Roberts, Reginald S. Richardson
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Patent number: 5519034Abstract: Tetrahydroisoquinoline compounds of formula I ##STR1## and pharmaceutically acceptable salts and lipophilic ester thereof have utility as analgesics and in the treatment of psychoses, Parinson's disease, Lesch-Nyan syndrome, attention deficit disorder or cognitive impairment or in the relief of drug dependence or tardive dyskinesia.Type: GrantFiled: August 18, 1994Date of Patent: May 21, 1996Assignee: The Boots Company PLCInventors: Antonin Kozlik, Bruce J. Sargent, Patricia L. Needham
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Patent number: 5519036Abstract: The invention relates to cyclic derivatives of general formula ##STR1## wherein R.sub.a, R.sub.b, X and Y are as defined in claim 1, the tautomers, the stereoisomers including the mixtures thereof and the salts thereof, particularly the physiologically acceptable salts thereof with organic or inorganic acids or bases, which have valuable pharmacological properties, preferably aggregation-inhibiting effects, pharmaceutical compositions containing the compounds and processes for preparing them.Type: GrantFiled: February 22, 1994Date of Patent: May 21, 1996Assignee: Karl Thomae GmbHInventors: F. Himmelsbach, Helmut Pieper, Volkhard Austel, Gunter Linz, Brian Guth, Thomas Muller, Johannes Weisenberger
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Patent number: 5516913Abstract: Novel alcohols of the formula ##STR1## wherein R.sup.a is azido or phthalimido, R.sup.4 is alkyl, cycloalkyl, cycloalkylalkyl, aryl or aralkyl, R.sup.7 and R.sup.8 together are a trimethylene or tetramethylene group which is optionally substituted by hydroxy, alkoxycarbonylamino or acylamino or in which one --CH.sub.2 -- group is replaced by --NH--, --N(alkoxycarbonyl)--, --N(acyl)-- or --S-- or which carries a fused cycloalkane, aromatic or heteroaromatic ring, and R.sup.9 is alkoxycarbonyl, monoalkylcarbamoyl, monoaralkylcarbamoyl, monoarylcarbamoyl or a group of the formula ##STR2## in which R.sup.10 and R.sup.11 each is alkyl, are described along with a process for their manufacture. These alcohols are useful as intermediates, for example in the manufacture of amino acid derivatives having antiviral activity.Type: GrantFiled: May 12, 1995Date of Patent: May 14, 1996Assignee: Hoffmann-La Roche Inc.Inventors: Kevin E. B. Parkes, Sally Redshaw, Gareth J. Thomas
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Patent number: 5514700Abstract: There are disclosed various compounds of the formula below, ##STR1## where n, X and R.sub.1 through R.sub.4 are as defined in the specification, which are useful for alleviating various memory dysfunctions characterized by a cholinergic deficit such as Alzheimer's disease.Compounds of this invention also inhibit monoamine oxidase and/or act at central .alpha..sub.2 -adrenergic receptors, and hence are useful as antidepressants.Type: GrantFiled: June 7, 1995Date of Patent: May 7, 1996Assignee: Hoechst-Roussel Pharmaceuticals IncorporatedInventors: Helen H. Ong, Gerard J. O'Malley, Michael C. Merriman, Mark G. Palermo
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Patent number: 5510379Abstract: .beta.-Carboxy sulfonates of the formula ##STR1## wherein R.sub.1 is aryl, R.sub.3 and R.sub.4 are hydrogen or alkyl, Y is -O-, -S-, or -NR.sub.2 -, and R.sub.5 is alkyl or aryl are potent inhibitors of the enzyme acyl CoA:cholesterol acyltransferase (ACAT) and are thus useful for treating hypercholesterolemia and atherosclerosis.Type: GrantFiled: December 19, 1994Date of Patent: April 23, 1996Assignee: Warner-Lambert CompanyInventors: Helen T. Lee, Joseph A. Picard, Drago R. Sliskovic
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Patent number: 5502060Abstract: Oligopeptide analogs are described. These compounds are useful in the inhibition of HIV protease, the prevention or treatment of infection by HIV and the treatment of AIDS, either as compounds, pharmaceutically acceptable salts, pharmaceutical composition ingredients, whether or not in combination with other antivitals, immunomodulators, antibiotics or vaccines. Methods of treating AIDS and methods of preventing or treating infection by HIV are also described.Type: GrantFiled: October 25, 1994Date of Patent: March 26, 1996Assignee: Merck & Co., Inc.Inventors: Wayne J. Thompson, Arun K. Ghosh, Joel R. Huff, Hee Y. Lee
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Patent number: 5498717Abstract: This invention relates to novel 6,7-dialkoxy-3,4-dihydroisoquinolin-8-ols, a process for preparing the 6,7-dialkoxy-3,4-dihydroisoquinolin-8-ols reioselectively and in a high yield utilizing the Bischler-Napieralski reaction, a process for synthesizing 6,7-dialkoxy-1,2,3,4-tetrahydroisoquinolin-8-ols via the compounds, and use of the 6,7-dialkoxy-3,4-dihydroisoquinolin-8-ols for preparation of the 6,7-dialkoxy-1, 2,3,4-tetrahydroisoquinolin-8-ols.It is possible according to this invention, to obtain the 6,7 -dialkoxy-1,2,3,4-tetrahydroisoquinolin-8-ols, which have hitherto been difficult to synthesize, via the 6,7-dialkoxy-3,4-dihydroisoquinolin-8-ols in a high yield.Type: GrantFiled: August 10, 1994Date of Patent: March 12, 1996Assignee: Banyu Pharmaceutical Co., Ltd.Inventors: Kiyofumi Ishikawa, Takashi Hayama
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Patent number: 5491149Abstract: This invention relates to substituted dihydroxypropylamines, a process to prepare intermediates useful for the synthesis of these compounds, compositions comprising such compounds, and a method of treating retroviral infection.Type: GrantFiled: August 26, 1994Date of Patent: February 13, 1996Assignee: The Du Pont Merck Pharmaceutical CompanyInventor: Prabhakar K. Jadhav
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Patent number: 5489686Abstract: This invention relates to novel substituted 1,2,3,4-tetrahydroisoquinolines which are useful in the treatment of vascular restenosis, various disorders of the central nervous system, in the regulation of female reproductive functions, in cognitive enhancement, in atherosclerosis and in treating excessive AVP secretory disorders. Novel intermediates useful in the preparation of the compounds are also disclosed. Methods of using the compounds and pharmaceutical compositions containing them are disclosed.Type: GrantFiled: April 28, 1994Date of Patent: February 6, 1996Assignee: Warner-Lambert CompanyInventors: Clifton J. Blankley, John C. Hodges, Sylvester Klutchko